possible to synthesize these materials from the reaction of
2a or 3a with 1 and not through the reaction of 1a with 2 or
3 which suggests steric constraints as a possible rationale
for the selectivity as the environment of the carbonyl of the
imidazole carboxylic esters change quite considerably.
The selectivity was studied further using 1,4-pentanediol,
4, which contains both primary and secondary alcohol sites.
When reacting 1a with 4, carbonate formation was predomi-
nantly at the primary alcohol site but an approximately 20%
reaction could be detected at the secondary hydroxyl.
However, when reacting 2a and 3a with 4, there was no
carbonate formation at the secondary hydroxyl and reaction
at the primary site only has been seen even if 2a and 3a are
present in large excesses and the mixture is refluxed for
several hours, Scheme 2.
Carbonate formation in triols8 was studied via the reaction
of 2a and 3a with 8 and 5. In the case of 8 the reaction of
the imidazole carboxylic esters gave 100% yield of carbon-
ates via reaction at the primary hydroxyl groups without
reaction at the secondary hydroxyl, but the reaction of 2a
and 3a with 5 did not proceed as expected. To simplify the
reaction, two diols, 1,2- and 1,3-propanediol (6 and 7), were
chosen as models for 5 and were reacted with 2a and 3a. In
both cases, the reaction with 7 proceeded as expected with
the formation of the bis-carbonate; however, when 2a or 3a
was reacted with 6, propylene carbonate was formed and
the corresponding alcohols 2 or 3 were recovered. We believe
that the cyclic carbonate formation proceeds via the selective
reaction of 2a or 3a at the primary hydroxyl followed by an
intramolecular substitution involving the neighboring sec-
ondary hydroxyl. The cyclization appears to be structure
dependent and reliant on 1,2-substitution as the synthesis of
the hydroxy carbonates of 4 and 8 and biscarbonates of 7
show no cyclic carbonate formation.
Scheme 2
The imidazole carboxylic ester 3a was also reacted with
tetrol 9 and amino diol 10. The bis-cyclic carbonate 11 was
synthesized as expected with evidence of cyclization derived
1
from the comparison of the H and 13C NMR spectra of 9
and 11. The 1H NMR (CD3OD) spectrum of the starting tetrol
9 shows two complex peaks: one at δ ) 1.60 ppm
corresponding to the (CH2)4 unit and a further peak at δ )
3.64 ppm which has been assigned as the CH(OH)CH2(OH)
diol groups. The CH(OH) and CH2(OH) are also easily
detected in the 13C DEPT (CD3OD) spectrum at δ ) 73.68
and 67.88 ppm, respectively. The 1H NMR (CDCl3) spectrum
of 11 however showed a marked simplification of the
previously complex signal of the diol groups. Three peaks
are now present at δ ) 3.98 (t, 1H, CH(H)), 4.44 (t, 1H,
CH(H)), and 4.61 ppm (m, 1H, CH(R)), indicating the
inequivalence of the CH2 protons in the cyclic carbonate ring.
The 13C signals for both carbons were also shifted signifi-
cantly. Small signals are present in the spectrum for
Evidence of selectivity is found in the API-MS examina-
1
tion of the products.8 More conclusively, H and 13C NMR
spectra confirm that no reaction occurs at the secondary
hydroxyl as carbon and proton signals for the R2CH-OH
group of 4 remain unchanged after reaction. For example,
the spectra of 4 are compared with those of 13 and 15 in
Table 3. 13C assignments were confirmed by DEPT spectra.
incomplete reaction which aids the interpretation of the 13
spectra with respect to the change of NMR solvent. The 13
C
C
(CDCl3) signals for the diol unit of unreacted tetrol 9 are
very similar to those of the spectrum run in CD3OD and are
at δ ) 74.17 and 67.31 ppm. The cyclic carbonate shows
signals at δ ) 77.07 and 69.57 ppm. The carbonate carbonyl
is also present at δ ) 155.34 ppm, confirming carbonate
formation.
Table 3. 1H and 13C NMR Evidence for Selective Carbonate
Formation with Imidazole Carboxylic Esters
If the reaction had proceeded with carbonate formation
only at the primary alcohol, we would have expected to still
see a complex 1H NMR spectrum and only marked changes
for the CH2(OH) 13C signal.
The synthesis of the amino cyclic carbonate 12 also
proceeded without complication and shows an unexpected
additional selectivity as there was no detectable reaction with
the secondary amine functionality.
Selective carbonate formation using 3a provides an easy
and single-step selective t-Boc protection of the primary
hydroxyl which would normally be achieved using reagents
such as t-Boc anhydride followed by careful separation of
the three possible products.
In summary, we have identified a series of new structure-
specific selective reactions using well-known reagents. The
imidazole carboxylic esters formed by the reaction of 1,1′-
carbonyldiimidazole and either secondary or tertiary alcohols
will react selectively with primary hydroxyls in polyols
Org. Lett., Vol. 1, No. 6, 1999
935